Antiviral efficacy, tolerability and pharmacokinetics of efavirenz in an unselected cohort of HIV-infected children.
Antiviral efficacy, tolerability and pharmacokinetics of efavirenz in an unselected cohort of HIV-infected children.
复制标题
依非韦伦在未经选择的 HIV 感染儿童队列中的抗病毒功效、耐受性和药代动力学。
DOI：
--
复制
发表时间：
2008
影响因子：
5.2
通讯作者：
D. Burger
中科院分区：
文献类型：
--
作者：
U. Wintergerst;F. Hoffmann;A. Jansson;G. Notheis;K. Huss;M. Kurowski;D. Burger
OBJECTIVES
To obtain data on the pharmacokinetics of efavirenz in children in clinical practice.
METHODS
HIV-1-infected children received efavirenz capsules or tablets in accordance with manufacturer's dosing recommendations. Plasma was collected at regular visits and analysed by HPLC. The therapeutic range of efavirenz was defined as 1.0-4.0 mg/L.
RESULTS
Thirty-three children were included. Median (range) age, body weight, dose and dose/kg were 8.2 (2.1-16.7) years, 24 (12-62) kg, 300 (200-800) mg and 13.3 (9.7-22.5) mg/kg, respectively. Median (range) efavirenz plasma concentration at first sampling was 2.8 (0.13-11.6) mg/L. Plasma concentrations were not dependent on age (P = 0.97) or dose/kg (P = 0.87). A total of 307 efavirenz plasma concentrations were determined. Forty-five samples (14.7%) contained >4.0 mg/L, and 27 samples (8.8%) contained <1.0 mg/L. Eight children (24%) reported persistent adverse events probably caused by efavirenz [concentration problems (5), sleep disorder (1), psychotic reaction (1) and seizure (1)]; six discontinued efavirenz for this reason. A non-significant trend existed towards a higher proportion of toxic efavirenz plasma concentrations (>4.0 mg/L) in subjects who reported efavirenz adverse events: 25.9% versus 12.8% (P = 0.23; t-test). Viral load was <50 copies/mL in all 27 subjects who continued efavirenz, despite occasional subtherapeutic efavirenz plasma concentrations in 12 children. The occasional subtherapeutic levels suggest that temporal non-adherence was present.
CONCLUSIONS
Efavirenz as part of highly active antiretroviral therapy was highly effective in children able to tolerate the drug. Therapeutic drug monitoring (TDM) as part of toxicity management may prevent discontinuation in a subset of patients. Temporal non-adherence occurs frequently. TDM may allow initiation of adherence interventions before viral load becomes detectable.
